The overall objectives of this intra-and interdepartmental program project research grant are the elucidation of the biochemical and pathophysiological characteristics of cystic fibrosis. Studies of human submandibular secretions have resolved 21 proteins, most of which have been identified. Quantitative studies demonstrate the primary difference between normal and CF secretions to be a 3 - fold elevation of gamma-amylase in the CF secretion. The 4 isoamylases have been isolated and carbohydrate differences determined. Further chemical characterization of the isoamylases from normal and CF donors are planned. The sodium reabsorption inhibition by CF combined sublingual saliva is being used in the development of an isolation procedure for the inhibitory factor(s). Attempting to decrease the variability of the assay, the inhibition by poly-l-lysine is being studied in more detail. Culturing of explants of respiratory epithelium and analysis of the secreted mucous glycoproteins has demonstrated CF secretions to have an increased sialic acid content and sialic acid/fucose ratios, an increased degree of sulfation, an increased virus hemagglutination inhibition, and decreased titers of blood group specific substance. The site and mechanism of sulfation will be investigated. In vitro immunoglobulin biosynthesis by peripheral blood lymphocytes and by respiratory epithelium continues to be studied. Additional characterization of a novel immunoglobulinlike protein secreted by tracheal explants is planned. Correlative studies of the pyocine types of P. aeruginosa from CF patients with the patient's clinical status suggests that infection with pyocine types N-1 and N-4 results in less morbidity. Additional studies on the effect of cystic fibrosis on the phagocytic and bacterial killing capabilities of the alveolar macrophage are planned along with a further development of studies of the alveolar macrophage plasma membrane.